Obstructive sleep apnea is a common disorder of obese middle-age men. It is due to airflow obstruction that results when the pharyngeal airway collapses during sleep. While the mechanism for collapse is not clear, we have developed the concept that the upper airway functions as a collapsible conduit (Starling resistor). In both human and animal studies, we have demonstrated airflow dynamics that are comparable to those in a simple collapsible conduit (Starling resistor). Specifically, collapse occurs at a discrete flow-limiting site (FLS) that obstructs airflow during sleep. Moreover, we have shown that increases in the collapsibility of the FLS lead to reductions in airflow during sleep. In the current proposal, this work will be extended to determine more precisely the factors that modulate airway collapsibility at the FLS. Specifically, it is now recognized that the FLS can occur in either the oropharynx or nasopharynx. Although the reason for variability in the location of the FLS is not clear, it can be assumed that the FLS occurs in the most collapsible pharyngeal segment. The major hypothesis of this proposal is that the collapsibility of the oropharynx and nasopharynx is modulated differently by pharyngeal structures and muscles. In Specific Aim #1, we will determine the structural basis for the location and collapsibility of the FLS in studies in the isolated feline upper airway. In Specific Aim #2, we will determine the mechanism for alterations in the location and collapsibility of the FLS when neuromuscular activity is stimulated. In each specific aim, mechanisms controlling the collapsibility in specific pharyngeal segments will be elucidated in the isolated feline upper airway. Studies will then be extended in humans to determine the structural and neuromuscular basis for abnormalities in upper airway function in apneic patients. This proposal builds on similarities in pharyngeal airflow dynamics in the cat and sleeping human to determine the role of adiposity in the pathogenesis of upper airway obstruction during sleep.